A short peptide with selective anti-biofilm activity against Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing bacteria

Cardoso, Marlon Henrique; Santos, Viviane P.M.; Costa, Bruna O.; Buccini, Danieli Fernanda; Rezende, Samilla B.; Porto, William F.; Santos, M.J.; Ribeiro, Suzana Meira; Franco, Octávio Luiz

doi:10.1016/j.micpath.2019.103605

Cited by 7 publications

(2 citation statements)

References 38 publications

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“…Although human erythrocytes is the most frequent choice for the preliminary in vitro testing of the haemolytic activity of AMPs intended for human use, it is not infrequent that erythrocytes sourced from other species are employed in the early screening phase. Several examples are available in the literature where AMPs targeting standard bacterial strains or human pathogens are tested against red blood cells collected from rodents 21 – 24 , or other mammalian species 25 – 27 . In addition, AMPs targeting veterinary pathogens are often tested for their haemolytic activity against human red blood cells 28 , 29 .…”

Section: Introductionmentioning

confidence: 99%

Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides

Greco

Molchanova

Holmedal

et al. 2020

Sci Rep

234

155

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the use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50-500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2-8 × MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general. Antimicrobial peptides (AMPs) have attracted great interest in clinical research over the past three decades as potential therapeutic agents against multidrug resistant bacteria. AMPs are produced by most living organisms and they act as host defense peptides by providing a rapid first line of defense against pathogens 1,2. They come in a variety of sizes and shapes but they are generally cationic and consist of less than 50 amino acids with antimicrobial activities in the low micromolar range 1,3. The discovery that the natural peptides often can be significantly simplified with maintained biological activities makes them plausible candidates for the development of antimicrobials 4-7. Currently, 36 antimicrobial peptides are undergoing preclinical and clinical phase 8 and almost 10,000 papers have been published in 2019 on AMPs. While several natural lipo-and glycopeptides, e.g. colistin and vancomycin, have been approved by the Food and Drug Administration (FDA) as antibiotics, AMPs have yet to make a significant impact on the drug market despite often being heralded as a promising option for the future treatment of drug resistant bacterial and fungal infections 9. AMPs are inherently not metabolically stable and their short half-lives and poor oral bioavailability, combined with potential toxic side effects

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Section: Introductionmentioning

confidence: 99%

Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides

Greco

Molchanova

Holmedal

et al. 2020

Sci Rep

234

155

View full text Add to dashboard Cite

show abstract

“…Pathogen resistance to antimicrobials, especially multi-drug resistance, poses a serious worldwide public health concern due to the higher morbidity and mortality rates caused by these infections. Alternatives to antimicrobials such as AMPs attract attention due to their multifactorial mechanism of action, low propensity to select for bacterial resistance, intracellular antibacterial activity, and special synergistic with conventional antimicrobials, among other advantages (Travis et al, 2018 ; Wang et al, 2018 ; Cardoso et al, 2019b ; Lazzaro et al, 2020 ; Ageitos et al, 2022 ; Aminov, 2022 ; Hao et al, 2022 ; Zhu R. et al ). Thus, the discovery, modification, reformation and de novo design of AMPs represent an exciting approach for infection management and control.…”

Section: Discussionmentioning

confidence: 99%